Structure of fibroblast growth factor 9 shows a symmetric dimer with unique receptor- and heparin-binding interfaces

Fibroblast growth factors (FGFs) constitute a family of at least 20 structu rally related heparin-binding polypeptides active in regulating cell growth , survival, differentiation and migration. FGF9, originally discovered as a glia-activating factor, shares 30% sequence identity with other FGFs and h as a unique spectrum of target-cell specificity. FGF9 crystallized in the t etragonal space group I4(1), with unit-cell parameters a = b = 151.9, c = 1 17.2 Angstrom. The structure of the glycosylated protein has been refined t o an R value of 21.0% with R-free = 24.8%) at 2.6 Angstrom resolution. The four molecules in the asymmetric unit are arranged in two non-crystallograp hic dimers, with the dimer interface composed partly of residues from N- an d C-terminal extensions from the FGF core structure. Most of the receptor-b inding residues identified in FGF1- and FGF2-receptor complexes are buried in the dimer interface, with the beta8-beta9 loop stabilized in a particula r conformation by an intramolecular hydrogen-bonding network. The potential heparin-binding sites are in a pattern distinct from FGF1 and FGF2. The ca rbohydrate moiety attached at Asn79 has no structural influence.